The Role of Exercise-Periodic-Breathing (EPB) in Impaired Ventilation Regulation Dysfunction in Heart Failure Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2010 by Chang Gung Memorial Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier:
NCT01454128
First received: October 14, 2011
Last updated: October 17, 2011
Last verified: September 2010
  Purpose

Heart failure (HF) is a complex syndrome characterized by myocardial dysfunction and an impaired regulatory function of multiple organ systems which were resulted from impaired cardiac output and consequently impaired perfusion of target organ. In cardiopulmonary exercise test (CPET), the investigators found there is periodic oscillation in minute ventilation of some patient. With periodic breathing (PB), clear oscillations in oxygen uptake, carbon dioxide output, tidal volume and left ventricle ejection fraction (LVEF) were also noted. Exertional hyper-ventilation that is caused by HF may further induce vasoconstriction during exercise and lead to further dysfunction of end-organ and muscle. Reduced end-organ perfusion/oxygenation may critically limit exercise performance. Hypoxic change during nadir phase of PB may deteriorate the exercise limitation. Physical training can have beneficial effects which can effectively counteract the progression of deleterious compensatory mechanisms of HF. Whether exercise yields the same beneficial effect on ventilation oscillation and inefficacy is not clear.

The investigators will observe the real-time cardiac and hemodynamic change respond to exercise with periodic breathing change. The investigators expect that these results obtained from this study can aid in determining appropriate exercise intervention to improve aerobic fitness as well as simultaneously improve hemodynamic control in patients with HF. A quasi-experimental design will be used in this investigation. 60 HF patients will be recruited from Chang Gung Medical Foundation, Keelung Branch after they have provided informed consent. These subjects will be divided into PB (n=30) and non-PB groups (n=30) by their expression of CPET. Patients from each groups received the same therapy and trace course for 2years including CV clinics, CPET and polysomnography. The investigators will measure subjects' physical fitness, oxygen transport and utilization of exercising skeletal muscles, cardiovascular functions and hemodynamics, blood cell parameters, RBC deformity and aggregation, plasma biomarkers of myocardial damage, oxygen stress and quality of life at pre-training stage and following the 6th , 12th, 18th, 24th months of the tracing program. Experimental results were analyzed by descriptive statistics, independent t-test, and repeated measure ANOVA. The investigators study the above parameter to realize the physiological response to exercise of these patients and discover the appropriate exercise intensity for prescription for EPB.


Condition Intervention
Impaired Oxygen Delivery
Ischemic Reperfusion Injury
Behavioral: exercise

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Role of Exercise-Periodic-Breathing in Impaired Ventilation Regulation Dysfunction in Patients With Heart Failure

Resource links provided by NLM:


Further study details as provided by Chang Gung Memorial Hospital:

Primary Outcome Measures:
  • VO2 max(maximal oxygen consumption) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    During cardiopulmonary exercise test, we could measure the value of patients' maximal oxygen consumption. It could represent the functional level of heart failure patient and be the mortality prediction.


Secondary Outcome Measures:
  • EPB pattern [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    We define the exercise periodic breathing pattern in primary cardiopulmonary exercise test(CPET). After exercise intervention, we analyze the ventilation picture again in follow up CPET. (EPB also a morality prediction )

  • All-cause mortality/CV morbidity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: April 2011
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Non-EPB
with exercise
Behavioral: exercise
36 session supervised exercise intervention
Other Name: cardiac rehabilitation
Experimental: EPB with exercise
with exercise
Behavioral: exercise
36 session supervised exercise intervention
Other Name: cardiac rehabilitation

Detailed Description:

Patients with heart failure display dyspnea on exertion, lower PCO2 and higher ventilatory response to exercise (V E -V CO 2slope), which demonstrated dysregulation of breathing in this disease category. Some of these patients develop further ventilation dysregulation pattern with ventilatory oscillation composed with exercise periodic breathing (EPB) and sleep apnea. Previous studies revealed the ventilatory oscillation was associated with cyclic changes in arterial oxygen (PO2) and carbon dioxide (PCO2) tensions, and also associated with severely impaired exercise tolerance, a steep V E -V CO 2slope, and low peak O 2 consumption, both correlated with the worse severity of heart failure and adverse prognosis. The origin of ventilatory oscillation might involved instability of the ventilator control system, which composed with prolonged circulatory delay, abnormal peripheral ergoreflex activation and peripheral chemo- and baro-sensitivity, even through abnormal autonomic reflexes to an altered central command. However, the most studies investigated these responses via sleep apnea under resting status especially those about brain. The real-time change response to exercise was limited to ventilatory parameters such as oxygen consumption, carbon dioxide production. Whether the exercise periodic breathing response to exercise which lead to abnormal cerebral hemodynamic responses to exercise in HF remain unclear.

Impaired cerebral blood flow was demonstrated during apnetic episode and related to neuropsychological deficits in sleep apnea patient. To be controlled by the same key feedback mechanism, impaired cerebral blood flow during exercise in EPB patients could be speculated. Moreover, Cerebral hypo-perfusion responses to exercise may contribute to the impairment of functional capacity in patients with HF. Accordingly, we hypothesize that the abnormal cerebral hemodynamics by exercise periodic breathing during exercise is associated with the decline of functional capacity in patients with HF. Besides, Physical training can have beneficial effects which can effectively counteract the progression of deleterious compensatory mechanisms of HF. Whether exercise yields the same beneficial effect on ventilation oscillation and inefficacy is not clear.

We will observe the real-time cardiac and hemodynamic change respond to exercise with periodic breathing change. We expect that these results obtained from this study can aid in determining appropriate exercise intervention to improve aerobic fitness as well as simultaneously improve hemodynamic control in patients with HF. A quasi-experimental design will be used in this investigation. Sixty HF patients will be recruited from Chang Gung Medical Foundation, Keelung Branch after they have provided informed consent. These subjects will be divided into PB (n=30) and non-PB groups (n=30) by their expression of CPET. Patients from each groups received the same therapy and trace course for 2years including CV clinics, CPET and polysomnography. We will measure subjects' physical fitness, oxygen transport and utilization of exercising skeletal muscles, cardiovascular functions and hemodynamics, blood cell parameters, RBC deformity and aggregation, plasma biomarkers of myocardial damage, oxygen stress and quality of life at pre-training stage and following the 6th , 12th, 18th, 24th months of the tracing program. Experimental results were analyzed by descriptive statistics (percentage, mean, and standard deviation), independent t-test, and repeated measure ANOVA. We study the above parameter to realize the physiological response to exercise of these patients and discover the appropriate exercise intensity for prescription for EPB.

This study employed simultaneously a noninvasive, bio-reactance device (i.e., noninvasive continuous CO monitoring system, NICOM) to assess cardiac hemodynamics, and a near-infrared spectroscopy (NIRS) to monitor changes in cerebral and muscular perfusion/oxygenation. We further elucidated the real-time adaption between ventilator parameter and hemodynamic ones during ventilation oscillation in patients with HF.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • cardiac event with optimal medial treatment within 3 months and have 4 more weeks spared from heart disease attack or major cardiac procedure.

Exclusion Criteria:

  • unstable angina pectoris
  • uncompensated heart failure
  • myocardial infarction during the past 4 weeks
  • complex ventricular arrhythmias
  • orthopedic or neurological limitations to exercise
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01454128

Contacts
Contact: Tieh-Cheng Fu, M.D 886-975360696 mr5598@adm.cgmh.org.tw

Locations
Taiwan
Dept of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital Recruiting
Keelung, Taiwan, 204
Contact: Tieh-Cheng Fu, M.D    886-975360696    mr5598@adm.cgmh.org.tw   
Principal Investigator: Tieh-Cheng Fu, M.D         
Sponsors and Collaborators
Chang Gung Memorial Hospital
Investigators
Principal Investigator: Tieh-Cheng Fu, M.D Chang Gung Memorial Hospital
  More Information

Publications:
Responsible Party: Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier: NCT01454128     History of Changes
Other Study ID Numbers: 99-2546B
Study First Received: October 14, 2011
Last Updated: October 17, 2011
Health Authority: Taiwan: Institutional Review Board

Keywords provided by Chang Gung Memorial Hospital:
exercise base rehabilitation
heart failure
periodic breathing
aerobic fitness

Additional relevant MeSH terms:
Heart Failure
Reperfusion Injury
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Postoperative Complications
Pathologic Processes

ClinicalTrials.gov processed this record on September 18, 2014